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| Status |
Public on Apr 10, 2024 |
| Title |
Translation initiation factor eIF1.2 orchestrates Toxoplasma gondii differentiation by regulating stage-specific gene expression |
| Organism |
Toxoplasma gondii |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Toxoplasma gondii persists in humans by converting from actively replicating acute stage tachyzoites to slow-growing chronic stage bradyzoites. The molecular mechanisms that mediate T. gondii differentiation remain poorly understood. Through a chemical mutagenesis screen, we identified translation initiation factor eIF1.2 as being critical for T. gondii differentiation. The presence of an F97L mutation in eIF1.2 identified in the screen or the complete lack eIF1.2 (∆eIF1.2) markedly impeded bradyzoite cyst formation in culture and in the brains of infected mice. ∆eIF1.2 parasites were defective in the upregulation of bradyzoite differentiation regulators BFD1 and BFD2 during stress-induced differentiation. Conditional overexpression of BFD1 or BFD2 rescued differentiation in ∆eIF1.2 parasites. We further show that eiF1.2 interacted with the yeast 40S ribosome and directed the scanning of a model 5’ untranslated region. Together, our findings imply that eIF1.2 functions by regulating the translation of key differentiation factors necessary to establish T. gondii chronic infection.
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| Overall design |
expression changes at the transcriptional and translational levels compared between parental and eIF1.2 knockout Toxoplasma gondii tachyzoites and 48h alkaline stressed parasites
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| Contributor(s) |
Holmes MJ, Sullivan WJ Jr |
| Citation(s) |
38782906 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI172752 |
Translation initiation factors driving persistence of Toxoplasma gondii bradyzoites in neurons |
INDIANA UNIVERSITY |
William J Sullivan |
| R21 AI167662 |
Regulation of cyst formation in the AIDS opportunistic pathogen Toxoplasma |
INDIANA UNIVERSITY |
William J Sullivan |
| R21 AI160610 |
Identifying novel players in Toxoplasma autophagy during chronic infection” |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
Vernon Bruce Carruthers |
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| Submission date |
Oct 19, 2023 |
| Last update date |
Jun 05, 2024 |
| Contact name |
Michael James Holmes |
| E-mail(s) |
[email protected]
|
| Organization name |
Indiana University School of Medicine
|
| Department |
Pharmacology & Toxicology
|
| Street address |
635 Barnhill Drive
|
| City |
Indianapolis |
| State/province |
IN |
| ZIP/Postal code |
46202 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL23466 |
Illumina HiSeq 4000 (Toxoplasma gondii) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA1029946 |
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